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Phosphorylation of Microtubule- Associated Protein 4 Promotes Hypoxic Endothelial Cell Migration and Proliferation

Endothelial cells play a critical role in the process of angiogenesis during skin wound healing. The migration and proliferation of endothelial cells are processes that are initiated by the hypoxic microenvironment in a wound, but the underlying mechanisms remain largely unknown. Here, we identified...

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Autores principales: Zhang, Junhui, Li, Lingfei, Zhang, Qiong, Yang, Xu, Zhang, Can, Zhang, Xingyue, Zhang, Dongxia, Lv, Yanling, Song, Huapei, Chen, Bing, Liu, Yao, Hu, Jiongyu, Huang, Yuesheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476958/
https://www.ncbi.nlm.nih.gov/pubmed/31040780
http://dx.doi.org/10.3389/fphar.2019.00368
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author Zhang, Junhui
Li, Lingfei
Zhang, Qiong
Yang, Xu
Zhang, Can
Zhang, Xingyue
Zhang, Dongxia
Lv, Yanling
Song, Huapei
Chen, Bing
Liu, Yao
Hu, Jiongyu
Huang, Yuesheng
author_facet Zhang, Junhui
Li, Lingfei
Zhang, Qiong
Yang, Xu
Zhang, Can
Zhang, Xingyue
Zhang, Dongxia
Lv, Yanling
Song, Huapei
Chen, Bing
Liu, Yao
Hu, Jiongyu
Huang, Yuesheng
author_sort Zhang, Junhui
collection PubMed
description Endothelial cells play a critical role in the process of angiogenesis during skin wound healing. The migration and proliferation of endothelial cells are processes that are initiated by the hypoxic microenvironment in a wound, but the underlying mechanisms remain largely unknown. Here, we identified a novel role for microtubule-associated protein 4 (MAP4) in angiogenesis. We firstly demonstrated that MAP4 phosphorylation was induced in hypoxic endothelial cells; the increase in MAP4 phosphorylation enhanced the migration and proliferation of endothelial cells. We also found that hypoxia (2% O(2)) activated p38/mitogen-activated protein kinase (MAPK) signaling, and we identified p38/MAPK as an upstream regulator of MAP4 phosphorylation in endothelial cells. Moreover, we showed that the promigration and proproliferation effects of MAP4 phosphorylation were attributed to its role in microtubule dynamics. These results indicated that MAP4 phosphorylation induced by p38/MAPK signaling promotes angiogenesis by inducing the proliferation and migration of endothelial cells cultured under hypoxic conditions via microtubule dynamics regulation. These findings provide new insights into the potential mechanisms underlying the initiation of the migration and proliferation of endothelial cells.
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spelling pubmed-64769582019-04-30 Phosphorylation of Microtubule- Associated Protein 4 Promotes Hypoxic Endothelial Cell Migration and Proliferation Zhang, Junhui Li, Lingfei Zhang, Qiong Yang, Xu Zhang, Can Zhang, Xingyue Zhang, Dongxia Lv, Yanling Song, Huapei Chen, Bing Liu, Yao Hu, Jiongyu Huang, Yuesheng Front Pharmacol Pharmacology Endothelial cells play a critical role in the process of angiogenesis during skin wound healing. The migration and proliferation of endothelial cells are processes that are initiated by the hypoxic microenvironment in a wound, but the underlying mechanisms remain largely unknown. Here, we identified a novel role for microtubule-associated protein 4 (MAP4) in angiogenesis. We firstly demonstrated that MAP4 phosphorylation was induced in hypoxic endothelial cells; the increase in MAP4 phosphorylation enhanced the migration and proliferation of endothelial cells. We also found that hypoxia (2% O(2)) activated p38/mitogen-activated protein kinase (MAPK) signaling, and we identified p38/MAPK as an upstream regulator of MAP4 phosphorylation in endothelial cells. Moreover, we showed that the promigration and proproliferation effects of MAP4 phosphorylation were attributed to its role in microtubule dynamics. These results indicated that MAP4 phosphorylation induced by p38/MAPK signaling promotes angiogenesis by inducing the proliferation and migration of endothelial cells cultured under hypoxic conditions via microtubule dynamics regulation. These findings provide new insights into the potential mechanisms underlying the initiation of the migration and proliferation of endothelial cells. Frontiers Media S.A. 2019-04-16 /pmc/articles/PMC6476958/ /pubmed/31040780 http://dx.doi.org/10.3389/fphar.2019.00368 Text en Copyright © 2019 Zhang, Li, Zhang, Yang, Zhang, Zhang, Zhang, Lv, Song, Chen, Liu, Hu and Huang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Zhang, Junhui
Li, Lingfei
Zhang, Qiong
Yang, Xu
Zhang, Can
Zhang, Xingyue
Zhang, Dongxia
Lv, Yanling
Song, Huapei
Chen, Bing
Liu, Yao
Hu, Jiongyu
Huang, Yuesheng
Phosphorylation of Microtubule- Associated Protein 4 Promotes Hypoxic Endothelial Cell Migration and Proliferation
title Phosphorylation of Microtubule- Associated Protein 4 Promotes Hypoxic Endothelial Cell Migration and Proliferation
title_full Phosphorylation of Microtubule- Associated Protein 4 Promotes Hypoxic Endothelial Cell Migration and Proliferation
title_fullStr Phosphorylation of Microtubule- Associated Protein 4 Promotes Hypoxic Endothelial Cell Migration and Proliferation
title_full_unstemmed Phosphorylation of Microtubule- Associated Protein 4 Promotes Hypoxic Endothelial Cell Migration and Proliferation
title_short Phosphorylation of Microtubule- Associated Protein 4 Promotes Hypoxic Endothelial Cell Migration and Proliferation
title_sort phosphorylation of microtubule- associated protein 4 promotes hypoxic endothelial cell migration and proliferation
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476958/
https://www.ncbi.nlm.nih.gov/pubmed/31040780
http://dx.doi.org/10.3389/fphar.2019.00368
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